Potassium Balance

Question 1

State the sources of potassium intake and output and the relative amounts

Answer 1

Intake -
Diet - 50 to 100 mmol/day

Output -
Urine - 45 to 112 mmols
Stools - 5 to 10 mmols
Sweat - 5mmols

Question 2

Describe the intra and extra cellular distrbution of K+ and what determines this

Answer 2

Intracellular distribution of K+ = 150 mmol/L average but some cells have higher [ ] such as muscle, liver, bone RBC and other cells
Extracellular distribution of K+ = 4.5 mmol/L
The distribution can be changed by insulin, adrenaline, pH and aldosterone (internal balance)

Question 3

State what acute and chronic potassium regulation is

Answer 3

• Acute regulation -
  Distribution of K+ between intra and extracellular fluid compartments
• Chronic regulation -
  Achieved by the kidney adjusting K+ excretion and reabsorption

Question 4

State the 3 main functions of potassium

Answer 4

1. Determines intracellular fluid osmolality - changes cell volume via osmosis
2. Determines resting membrane potential - very important for normal functioning of excitable cells
3. Affects vascular resistance

Question 5

Describe how the Na+/K+ pump works

Answer 5

• Na+/K+ ATPase pumps 3Na+ out of the cell and 2K+ ions into the cell
• This maintains the fact that more than 95% of bodily K+ is located intracellularly and only 2.5% in ECF - high intracellular [K+] and low intracellular [Na+]
• Energy to drive the pump is released by ATP hydrolysis

Question 6

Describe the internal balance/acute regulation of K+

Answer 6

• Extracellular fluid pool will change more dramatically with changes in body K+ distribution e.g. after a meal there is a slight increase in plasma [K+] which is shifted into the intracellular fluid compartment
• Shift is mainly subject to hormonal control- insulin, adrenaline, aldosterone and pH changes
• It is key that plasma [K+] remains in the right range

Question 7

What determines whether a person is hyper or hypo kalaemic?

Answer 7

Hyperkalaemia - plasma [K+] is above 5.5 mM

Hypokalaemia - plasma [K+] is below 3.5 mM

Question 8

Describe how resting potential is normally maintained

Answer 8

Membrane potential formed by creation of ionic gradients - combination of chemical and electrical gradients

Normal resting membrane potential is maintained by a dynamic balance between Na+ and K+ concentrations

Question 9

Describe how hypokalaemia and hyperkalaemia affect potential difference in a cell and what the significance is

Answer 9

• When [K+] outside the cell increases and the [K+] inside the cell is constant the nernst equilibrium potential increases and potential becomes more positive
• When [K+] outside the cell decreases and the [K+] inside the cell is constant the nernst equilibrium potential decreases and potential becomes more negative
• Relatively small changes in the [K+] extracellularly are enough to drastically change the potential difference in a cell so can severely affect cardiomyocyte membrane potential which causes changes in ECG

Question 10

Describe how ECG changes during hypokalaemia and hyperkalaemia

Answer 10

Hypokalaemia - decreased amplitude of T wave, prolonged QU interval and prolonged P wave

Hyperkalaemia - increased QRS complex, increased amplitude of T wave and loss of P wave

Question 11

Describe how hypokalaemia and hyperkalaemia affect action potentials

Answer 11

Lower (more negative) - low [K+] = hyperpolarisation - the cell is more negative than the resting potential so it takes more for it to reach the threshold potential for an action potential to propagate

Higher (less negative) - high [K+] = depolarisation - the cell is less negative than the resting potential so it takes less for the threshold potential to be reached and an action potential to propagate

Question 12

Describe what causes hypokalaemia

Answer 12

Caused by renal or extra renal loss of K+ or by restricted intake

E.g.
- Long standing use of diuretics without KCl compensation
- Hyperaldosteronism/conn’s syndrome which increase aldosterone secretion
- Prolonged vomiting = Na+ loss = increased aldosterone secretion = K+ excretion in kidneys
- Profuse diarrhoea

Question 13

State what hypokalaemia results in

Answer 13

• Decreased resting membrane potential
• Decreased release of adrenaline aldosterone and insulin

Question 14

Describe what causes hyperkalaemia

Answer 14

• Acute hyperkalaemia is normal during prolonged exercise
• Disease states -
• Insufficient renal excretion
• Increased release from damaged body cells e.g. during chemotherapy, long lasting hunger, prolonged exercise or severe burns
• Long term use of potassium sparing diuretics
• Addison’s disease - adrenal insufficiency

Question 15

What happens when plasma [K+] is above 7mM?

Answer 15

It is life threatening - asystolic cardiac arrest

Question 16

What is the treatment for hyperkalaemia?

Answer 16

• Insulin/glucose infusion used to drive K+ back into cells
• Insulin is extremely important - mechanism is unclear - may stipulate Na+/K+ pump
• Other hormones (aldosterone and adrenaline) stimulate Na+/K+ pump - increases cellular K+ influx

Question 17

In a healthy person what determines most of K+ balance?

Answer 17

The kidney

Question 18

What is the problem with K+ loss in stool?

Answer 18

K+ excretion in the stools is not under regulatory control e.g. large amounts can be lost by extra renal routes

Question 19

What is K+ homeostasis particularly important in now?

Answer 19

Increasingly important limiting factor in therapy for cardiovascular disease

Question 20

Which drugs increase serum [K+]?

Answer 20

Beta blockers, ACE inhibitors etc

Question 21

Describe overall what the kidneys do with Na+ and K+

Answer 21

• The human kidneys have evolved to conserve Na+ and excrete K+
• Na+ and K+ are filtered freely at the glomeruli
• Plasma and glomerular filtrate have the same [Na+] and [K+]
• In 24hr the glomerular filtrate contains 25 moles Na+ and 0.7 moles K+ but this depends on dietary intake

Question 22

Describe what happens to K+ in the proximal convoluted tubule including the mechanisms

Answer 22

• In proximal convoluted tubule -
• 60 to 70% Na+ and K+ reabsorbed in proximal convoluted tubule
• Fraction that is reabsorbed in proximal convoluted tubule is constant
• Absolute amount reabsorbed varies with glomerular filtration rate
• How does K+ move in the proximal convoluted tubule? -
• The Na+/K+ pump acts to pump Na+ ions out of the tubule epithelial cells into the ECF and pump K+ ions into it creating a low [Na+] intracellularly and a high [K+] intracellularly
• While there is passive diffusion of K+ ions back into the ECF there is still a high [K+]
• This creates a Na+ gradient which cause Na+ ions to enter the epithelial cells cotransporting amino acids, glucose and phosphates with them while another transporter (antiporter) transports H+ ions out of the epithelium into the tubular lumen
• There is then passive/paracellular transport of Cl-, K+ and Na+ ions from the tubular lumen which are then reabsorbed
• This occurs because removal of the other components from the tubular fluid (Na+, glucose, amino acids, phosphates) concentrates the K+ and Cl-

Question 23

Describe Na+/K+ movement in the loop of Henle including the mechanism

Answer 23

Na+/K+ movement in the loop of Henle -
- As the glomerular filtrate travels down the descending arm water freely diffuses out such that the filtrate becomes concentrated so it gets a much higher osmolarity
- As the filtrate ascends the ascending arm the NaCl initially diffuses out passively and then is pumped out which decreases osmolarity again to below the level it was when it entered the loop of Henle
- The transporter of Na+ and Cl- ions also transported K+ ions out of the loop of Henle’s ascending arm into the epithelial cells
- The movement of Na+ is again driven by the Na+/K+ ATPase which pumps 3Na+ ions out of the epithelial cells and into the ECF
- The K+ ions then diffuse from the epithelial cells into the ECF

Question 24

Describe K+ movement in the DCT and the mechanism

Answer 24

K+ movement in the distal convoluted tubule -
- More than 90% of filtered K+ is reabsorbed in the PCT and loop of Henle
- Excretion of K+ into urine by overload is controlled by K+ secretion by principal cells of late DCT and CD
- The Na+/K+ ATPase pumps 3Na+ ions out of the epithelial cells into the ECf and 2K+ ions into the epithelial cells from the ECF
- K+ ion would then usually diffuse from the epithelial cells into the ECF but they can enter the tubular lumen instead
- This occurs when ENaC channels (epithelial Na channels) also Na+ ions to move down the gradient from the tubular lumen into the epithelial cells
- There is also a second mechanism by which there is a symporter which transports both Cl- ions and K+ ions from the principal cells into the lumen

Question 25

Describe what determines K+ secretion in DCT and how it is achieved briefly

Answer 25

* Determinants of K+ secretion in distal convoluted tubule - - Increased K+ intake - Changes in blood pH - Alkalosis - increased excretion of K+ which decreases serum [K+] - Acute acidosis - decreased excretion of K+ which increases serum [K+] * How is this achieved? - - Activity of Na+/K+ ATPase pump - Electrochemical gradient - Permeability of luminal membrane channel

Question 26

How does aldosterone increase secretion after increasing plasma [K+]? (3 ways)

Answer 26

1. Slows exit from basolateral membrane which increases [K+] which produces a cell-lumen concentration gradient 2. Increased activity of Na+/K+ ATPase which increases the [K+] inside the epithelial cells of the tubule which then increases movement of K+ into the tubular lumen 3. Stimulates aldosterone secretion

Question 27

Describe how aldosterone has its effects

Answer 27

1. There is an increased intake of potassium 2. This increases the plasma [K+] 3. This causes increased aldosterone secretion from the adrenal cortex 4. This increases the plasma [aldosterone] which causes collecting ducts to increase K+ secretion 5. The increased plasma K+ also directly causes the cortical collecting ducts to increase their K+ secretion 6. Subsequently K+ excretion is increased

Question 28

What does aldosterone act to do?

Answer 28

* Increase the activity of the Na+/K+ pump which then - - Increases K+ influx - Increases [K+] - Produces a cell-lumen concentration gradient * Increases ENaC channels which then - - Increases Na+ reabsorption - This decreases cell negativity and increases lumen negativity - This then produces a voltage gradient Redistributes ENaC from intracellular localisation to membrane Also increases permeability of luminal membrane K+

Question 29

State and describe other factors that affect K+ secretion

Answer 29

* Alkalosis and acidosis - - In a high pH environment (alkalosis) the activity of the Na+/K+ pump is elevated so there is an increase in the intracellular [K+] which favours its secretion to the tubular lumen - In a low pH environment (acidosis) the activity of the Na+/K+ pump is decreased so there is a decrease in the intracellular [K+] which decreases its secretion to the tubular lumen * Tubular flow rate and K+ secretion - - Increased flow rate can be caused by an increased glomerular filtration rate, an inhibition of reabsorption and K+ wasting diuretics - This essentially dilutes the potassium as it is being moved away from cells at a faster rate so the electrochemical gradient is favoured and more K+ ions enter the tubular lumen from the epithelial cells - ADH impacts K+ ion channels allowing more K+ to be secreted into the tubules * Reabsorption of K+ in severe hypokalaemia - - Intercalated cells of the late DCT and CD become active - This provides additional reabsorption of K+ to preserve its [ ] - Mechanism not well known by it activates a K+/H+ ATPase which pumps K+ ions into cells from the tubular lumen and pumps H+ ions into the lumen - This increases the intracellular [K+] so K+ is transported from the cells into the ECF

Question 30

Describe how Na+/K+ balance maintains K+ when ECF volume changes

Answer 30

- There is a decrease in the ECF volume - This causes increases aldosterone secretion from the adrenal cortex - Aldosterone then promotes K+ secretion/excretion in the cortical collecting ducts - The decrease is ECF volume and aldosterone will also cause the proximal tubule to increase Na+ reabsorption so there is a reduced flow rate in the tubules - Such that there is an unchanged K+ excretion

Question 31

Describe the renin angiotensin aldosterone system and how it impacts Na+ and K+ when BP and Na+ decrease

Answer 31

E.g. If there was a decrease in BP (detected by juxtaglomerular apparatus) and decrease in Na+ (detected by macula densa) - This would signal the release of renin which would release of angiotensin II which causes vasoconstriction to increase BP again - The angiotensin II also acts on the adrenal cortex along with the high [K+] in the plasma to increase secretion of aldosterone - In principal cells of the DCT and CD promotes H2O and Na+ reabsorption and K+ secretion - In intercalated cells it promotes Na+ and K+ reabsorption and H+ secretion

Question 32

What hormones does the adrenal cortex produce?

Answer 32

Produces: - Glucocorticoid hormones - Sex hormones - Mineralocorticoid hormones

Question 33

Describe Addisons disease (cause, what it leads to, treatment)

Answer 33

- A primary adrenal insufficiency - Rare compared to secondary adrenal insufficiency - Damage to the cortex leads to reduced hormone production and numerous symptoms - Deficiency in aldosterone causes the body to secrete large amounts of Na+ which leads to low serum [Na+] so the body retains K+ and has hyperkalaemia - Treatment usually involves steroid replacement therapy for life

Question 34

Describe what happens in secondary adrenal insufficiency

Answer 34

- The pituitary secretion of ACTH decreases - This reduces levels of cortisol - Causes the adrenal glands to shrink

Question 35

Describe what Conns syndrome is

Answer 35

* Primary aldosteronism aka conn's syndrome - - This is due to aldosterone producing adenoma of the adrenal gland zona glomerulosa - It is usually less than 3cm, unilateral and renin unresponsive - no control mechanism - Hyperaldosteronism (excess release of aldosterone) due to variety chronic disease - Most commonly (50-60%) due to conn's syndrome remaining 40-50% due to bilateral adrenal hyperplasia - Aldosterone release in absence of stimulation by angiotensin II

Question 36

What is the mechanism behind the condition?

Answer 36

- There is greatly increased plasma aldosterone which causes the kidneys to stimulate Na+ reabsorption and K+ excretion so the person develops hypertension and has increased fluid volume - causes hypokalaemia, hypernatremia and alkalosis (decreased K+, increased Na+ and increased pH) - There is increased BP and Na delivery to the macula densa which decreases the release of renin - renin independent hypertension

Question 37

What is the treatment for Conns disease?

Answer 37

- Surgical removal of tumour containing adrenal gland - Hypertension and hypokalaemia controlled with K+ sparing agents e.g. spironolactone